Téllez S., López C., Sujka E., Martínez A. LIPIDOS TOLEDO S.A. (LIPTOSA) FEED ADDITIVES 2017, Frankfurt 29 th September 2017
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1 Téllez S., López C., Sujka E., Martínez A. LIPIDOS TOLEDO S.A. (LIPTOSA) FEED ADDITIVES 2017, Frankfurt 29 th September 2017
2 Antimicrbials are used in livestck prductin t maintain health and prductivity. These practices cntribute t the spread f drug-resistant pathgens in bth livestck and humans, psing a significant public health threat (Van Beckel et al., 2015). GLOBAL AND EMERGING PUBLIC HEALTH CRISIS OF ANTIBIOTIC RESISTANCE NEW POLICIES The practice withut using in fd animal prductin has been implemented in the Eurpean Unin cuntries since 2006 and mre cuntries are expected t fllw. Increasing regulatin f antimicrbial (treatment and prphylaxis) Current use f antimicrbial in livestck (THE REVIEW ON ANTIMICROBIAL RESISTANCE, 2015)
3 Antimicrbials in swine prductin Evlutin f PCU in EU (EMA, 2016) New challenges in EU: Ban f the use f at medicinal levels in piglet feed. Significant reductin f use.
4 searching fr alternatives t antibitics: WITH similar antimicrbial and grwth-prmting effects prfitable results WITHOUT inducing: bacterial resistance and tlerance ptential side effects t animals txicity t humans residues in fds f animal rigin envirnment impact Organic acids, enzymes, prbitics, prebitics, antimicrbial peptides and phytgenic cmpunds (including essential ils, btanicals and herbal extracts) have been widely recgnized as ptential alternatives t antibitics in feed (Yang et al., 2015).
5 Essential ils (EOs) are armatic ily liquids btained frm plant material (flwers, buds, seeds, leaves, twigs, bark, herbs, wd, fruits and rts) (Burt, 2004; Cal et al., 2015) They can be btained by different methds: cld pressing, fermentatin, extractin r steam distillatin. EOs are highly cmplex mixtures f individual arma cmpunds: terpene cmpunds (mn-, sesqui- and diterpenes), alchls, acids, esters, epxides, aldehydes, ketnes, amines and sulfides. Cmpsitin f EOs depend n: Species and subspecies Part f the plant Harvesting seasn Gegraphical surce Extractin methd
6 ~ 3000 EOs are knwn, f which abut 300 are cmmercially imprtant. The greatest use f EOs in the EU is in fd/feed (as flavurings), perfumes and pharmaceuticals. GRAS (Generally Recgnized As Safe) ANTIMICROBIAL PROPERTIES:, antiviral, antimyctic, antitxigenic, antiparasitic and insecticidal Phenlic cmpnents Minr cmpnents Majr cmpnents f sme EOs that exhibit antibacterial prperties (Burt, 2004)
7 MODE OF ANTIBACTERIAL ACTION; Still nt cmpletely understd Hydrphbicity Main mechanisms f actin: (Faleir, 2011) Mechanisms f actin f essential ils and their cmpnents in a bacterial cell (adapted frm Burt 2004). Cell wall and membrane disturbance Leakage f cell cntents Alteratins n intracellular and external ATP balance Synthesis f heat shck prteins (HSPs) ph disturbance Intracytplasmic changes (cagulatin) Damage t DNA Activity anti-qurum sensing
8 EOs are mre active against Gram-psitive than Gram-negative bacteria (Burt, 2004) Determinatin f the antimicrbial activity Bacteristatic/ Bactericide Difficult (vlatile prperties, inslubility in water) Need fr develpment and implementatin f standardized tests in vitr Cmparisn f published data is cmplicated In vitr t in viv extraplatin f results Prtectin f EOs fr enhancing their antimicrbial effect
9 SYNERGISM BETWEEN: Different cmpnents f EOs whle EOs have a greater antibacterial activity than the sum f the individual effects f the different cmpnents EOs and antibitics EOs and
10
11 T evaluate the efficacy f a cmplementary feed based n a cmbinatin f essential ils and rganic acids against several respiratry, digestive and skin swine bacterial pathgens. Cmbinatin initially designed against S. suis. Include 6 EOs (including Origanum vulgare and Syzygium armaticum ils), rganic acids and their salts. VISAVET Health Surveillance Centre (Cmplutense University, Madrid) MIC determinatin by Brth Micr-Dilutin Methd (CLSI, 2013)
12 31 clinical strains (prcine rigin): BACTERIAL PATHOGEN STRAINS ORIGIN DISEASE/LESIONS Streptcccus suis Articulatin (n=2) Brain (n=7) Heart (n=2) MENINGITIS, ARTHRITIS, PNEUMONIA, ENDOCARDITIS Staphylcccus aureus Articulatin (n=4) EPIDERMITIS, ARTHRITIS Staphylcccus hyicus Haemphilus parasuis Articulatin (n=2) Brain (n=2) Heart (n=1) Lung (n=1) Brain (n=1) EXUDATIVE EPIDERMITIS GLÄSSER DISEASE Pasteurella multcida Lung (n=3) PNEUMONIA, PERICARDITIS, PLEURITIS Escherichia cli Actinbacillus pleurpneumniae Liver (n=2) Brain (n=2) Heart (n=1) Lung (n=1) SEPTICEMIA, COLIBACILOSIS, EDEMA DISEASE PNEUMONIA AND PLEURITIS
13 BACTERIAL PATHOGENS N. STRAINS Number f strains with MIC (mg/ml) f > 3 Staphylcccus aureus Staphylcccus hyicus MIC (average) (mg/ml) Streptcccus suis ,88 Haemphilus parasuis ,16 Pasteurella multcida Escherichia cli 4 4 > 3 A. pleurpneumniae 2 2 > 3 MIC 2 mg/ml MIC = 3 mg/ml MIC > 3 mg/ml Pasteurella multcida Haemphilus parasuis Streptcccus suis ** Nte: Gram +; Gram - Staphylcccus hyicus Staphylcccus aureus Escherichia cli Actinbacillus pleurpneumniae
14 Diversity f published data: (i) evaluatin methd, (ii) bacteria spp and islates (clinical r reference) and (iii) EO/EO cmpnent. PLANT OF ORIGIN MICRO-ORGANISM MIC VALUE (mg/ml) REFERENCE Origanum vulgare (Oregan) Syzygium armaticum (Clve) E. cli S. aureus Chuhan et al., 2017 S. aureus 1.25 De Suza et al., 2009 (frm Yang et al., 2015) S. aureus E. cli E. cli S. aureus E. cli S. aureus Da Silviera et al, 2011 (frm Yang et al., 2015) Burt, 2004 Jagadeesh Babu et al., 2011 E. cli Sengwei et al., 2009 (frm Yang et al., 2015) E. cli S. aureus Burt, 2004 N data fund abut specific swine pathgens The cmbinatin is effective against specific species f Gram + and - bacteria
15 Cnsideratins t take int accunt: In vitr t in viv extraplatin f MIC values Prtectin f EOs and rganic acids Pharmackinetics and pharmacdynamics (ral rute) Bacterial pathgenesis Selectin f in viv parameters t determine efficacy: Prevalence f disease/lesins/symptms Prductin indices Others Gd results in viv (data nt shwn) Reducing incidence f S. suis and H. parasuis in farms Imprving prductin parameters Trials currently running LIVER GALL BLADDER ESOPHAGUS LARGE INTESTINE ph SMALL INTESTINE ph APPENDIX PANCREAS RECTUM STOMACH ph
16 T evaluate the efficacy f a cmplementary feed based n a cmbinatin f essential ils and rganic acids against Brachyspira hydysenteriae. Include 5 EOs (including Origanum vulgare and Cinnammum zeylanicum ils), rganic acids and their salts. Animal Disease Diagnstics Center, Cllege f Veterinary Medicine, NCYU (Taiwan) MIC determinatin by Agar Dilutin Methd (CLSI, 2016) Strains: 56 clinical islates f Brachyspira hydysenteriae + B. hydysenteriae B-78 (ATCC 27164)
17 % islates BACTERIAL PATHOGEN N. STRAINS Number f islates with MIC (μg/ml) f Brachyspira hydysenteriae MIC50 = 250 μg/ml MIC90 = 500 μg/ml
18 Few published data t cmpare (due t its fastidius grwth characteristics) Vande Maele et al., 2015 MIC data expressed in mm. Best results: MCFA (capric and lauric acid) and essential il cmpnents (thyml, carvacrl and cinnamaldehyde). Verlinden et al., 2013 (Brachyspira intermedia) Best results: Cinnamaldehyde (MIC= 80 μg/ml), carvacrl and thyml (MIC= μg/ml) Gd results in viv (data nt shwn) Reducing incidence f disease in farms Imprving prductin parameters Trials currently running
19 Eubitics and phytgenic cmpunds have a gd ptential as an alternative t antibitics in feed fr fd animal prductin (Yang et al., 2015). The present study cnfirms the efficacy f a cmbinatin f essential ils and rganic acids against swine pathgens. Further studies are crucial in rder t determine the mst efficient cmbinatin f prtected essential ils and rganic acids, accrding t bacteria species and their pathgenesis. It is difficult t cnduct systematic and cmprehensive evaluatins tward the efficacy and safety f phytgenic cmpunds due t their cmplex cmpsitin (Yang et al., 2015). Better understanding f their mechanisms f actin and interactin with gut micrbita, gut physilgy and micrbilgy. Standardized efficacy methds in vitr, in viv GRAS evaluatin
20 Regulatin EC 1831/2003 Flavurings (2b): natural r crrespnding synthetic chemically define flavurings (f.e.: carvacrl) natural prducts btanically defined (f.e: Oregan il) RE-AUTHORIZATION maximum and recmmended levels, incmpatibilities, cntraindicatins, target species, etc. Other ztechnical additives (4d) HOLDER SPECIFIC AUTHORISATION
21 References available upn request
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